Screening for MYO15A gene mutations in autosomal recessive nonsyndromic, GJB2 negative Iranian deaf population

Abstract

MYO15A is located at the DFNB3 locus on chromosome 17p11.2, and encodes myosin-XV, an unconventional myosin critical for the formation of stereocilia in hair cells of cochlea. Recessive mutations in this gene lead to profound autosomal recessive nonsyndromic hearing loss (ARNSHL) in humans and the shaker2 (sh2) phenotype in mice. Here, we performed a study on 140 Iranian families in order to determine mutations causing ARNSHL. The families, who were negative for mutations in GJB2, were subjected to linkage analysis. Eight of these families showed linkage to the DFNB3 locus, suggesting a MYO15A mutation frequency of 5.71% in our cohort of Iranian population. Subsequent sequencing of the MYO15A gene led to identification of 7 previously unreported mutations, including 4 missense mutations, 1 nonsense mutation, and 2 deletions in different regions of the myosin-XV protein.

Whole-exome sequencing identifies MYO15A mutations as a cause of autosomal recessive nonsyndromic hearing loss in Korean families

“…Mutations that cause hearing loss were first identified at the DFNB3 locus, in residents of a village in Indonesia. Since then, many mutations have been reported from Pakistan, India, Turkey, Indonesia, and Brazil [5,7]. However, the two mutations identified in the present study are novel and are the first MYO15A mutations reported in East Asians.…”

“…Forty-three mutations have been reported in MYO15A , most of which have been found by linkage analysis in consanguineous families from specific countries, such as Pakistan, Turkey, and Iran [5-7]. Diagnostic testing for this gene is not routinely offered owing to its large size, and the frequency and spectrum of MYO15A mutations in most ethnic populations are not known.…”

Comprehensive genetic testing with ethnic‐specific filtering by allele frequency in a Japanese hearing‐loss population

“…In other studies of the Japanese population, GJB2 mutations were found in exceptionally high numbers, followed by mutations in SLC26A4, USH2A, GPR98 , or in CDH23, SLC26A4, MYO15A (16) (17). Comparisons across multiple populations are difficult due to variations in patient selection criteria and enrollment numbers, however mutations in MYO15A appear to be common in several areas of the world (18) (19). …”

Mutations in the MYO15A Gene Are a Significant Cause of Nonsyndromic Hearing Loss

“…1 The clinical features of ARNSHL (hearing level, age at onset, progressiveness, associated symptoms, etc) differ according to the causative gene/genotype. [4][5][6][7] These reports suggest that MPS screening of candidate genes is an effective and useful strategy. Comprising 66 exons and 71 kbp of DNA on chromosome 17p11.2, MYO15A encodes the 3530amino acid myosin XV protein.…”